Dichloromethane → N-(3-ethyl-1-((6-(piperazin-1-yl)pyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide trihydrochloride

HRID 79411Notes

Reaction equation

HRID 79411 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[N:30]=[C:29]([N:31]3[CH2:36][CH2:35][N:34](C(OC(C)(C)C)=O)[CH2:33][CH2:32]3)[CH:28]=[CH:27][CH:26]=2)[N:4]=1)[CH3:2].FC(F)(F)C(O)=O.[Cl:51]CCl>>[ClH:51].[ClH:51].[ClH:51].[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[C:29]([N:31]3[CH2:32][CH2:33][NH:34][CH2:35][CH2:36]3)[N:30]=2)[N:4]=1)[CH3:2]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 67262131tert-butyl 4-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 67260092N-(3-ethyl-1-((6-(piperazin-1-yl)pyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide trihydrochloride

Procedure

To a solution of tert-butyl 4-(6-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)pyridin-2-yl)piperazine-1-carboxylate (12 mg, 0.021 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (1 mL). The mixture was stirred for 1 hour at ambient temperature. The solution was concentrated under reduced pressure. The residue was re-dissolved in a mixture of dichloromethane and methanol and neutralized by the addition of ammonium hydroxide solution. The solvent was removed under reduced pressure. The residue was purified by preparative thin layer chromatography on silica, eluting with 15% methanol in dichloromethane containing 1% ammonium hydroxide solution. The isolated product was dissolved in a mixture of ethyl acetate, methanol and dichloromethane. Concentrated hydrochloric acid (2 drops) was added. Concentration under reduced pressure followed by high vacuum gave N-(3-ethyl-1-((6-(piperazin-1-yl)pyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide trihydrochloride (5.0 mg). MS (APCI), positive scan, m/z=481.3 (M+H).

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. dissolutionThe residue was re-dissolved in a mixture of dichloromethane and methanol
  3. additionneutralized by the addition of ammonium hydroxide solution
  4. customThe solvent was removed under reduced pressure
  5. customThe residue was purified by preparative thin layer chromatography on silica
  6. washeluting with 15% methanol in dichloromethane containing 1% ammonium hydroxide solution
  7. dissolutionThe isolated product was dissolved in a mixture of ethyl acetate, methanol and dichloromethane
  8. additionConcentrated hydrochloric acid (2 drops) was added
  9. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-f50cb0aed88e44e09ae5cd37ad04fad9
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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